Beta-tubulin and microtubule-associated proteins (TUBB/MAPs)

Beta-tubulin and microtubule-associated proteins (MAPs) are essential components of the eukaryotic cytoskeleton, primarily responsible for the formation and regulation of microtubules. Beta-tubulin, as part of the alpha/beta-tubulin heterodimer, serves as the structural subunit that polymerizes into microtubules, which are critical for mitosis, intracellular transport, and maintaining cell architecture [1.1.3, 1.3.1]. MAPs, such as Tau and MAP4, interact with these microtubules to regulate their stability, assembly, and spatial organization [1.2.1, 1.2.5]. This target system is a cornerstone of cancer chemotherapy, where drugs like taxanes and vinca alkaloids bind to beta-tubulin to either stabilize or destabilize microtubules, leading to mitotic arrest and apoptosis [1.1.4, 1.3.2]. Additionally, MAPs are significant in neurodegenerative diseases, most notably Alzheimer's disease, where the MAP Tau undergoes pathological hyperphosphorylation and aggregation [1.1.1, 1.2.5]. While beta-tubulin is the direct target for most clinical microtubule-targeting agents, MAPs are increasingly investigated as therapeutic targets and biomarkers for drug resistance [1.2.1, 1.2.3]. Therapeutic challenges include dose-limiting toxicities like peripheral neuropathy and the emergence of drug resistance through the expression of specific tubulin isotypes such as βIII-tubulin [1.1.1, 1.3.2].

Other names

β-tubulinMicrotubule-associated proteinsTubulinMicrotubule-targeting agents targetMAPs

Microtubule-targeting agents (MTAs) act by binding to specific sites on beta-tubulin to either stabilize microtubules (preventing depolymerization) or destabilize them (inhibiting polymerization), both of which disrupt the mitotic spindle and lead to cell cycle arrest and apoptosis [1.3.1, 1.3.2].